MEFANOR-D TABLETS (Each tablet contains Mefenamic Acid 250mg/ Dicycloverine HCL 10mg

Indications

• Symptomatic relief of gastrointestinal disorders characterized by smooth muscle spasm
• Irritable bowel syndrome
• Acute spasm in diagnostic procedures

Dosage

Children: Child 12–17 years: 10–20 mg three times a day. Child 2–4 years: 5 mg three to four times a day. Child 1 month–1 year: 300–500 micrograms/kg three to four times a day (maximum per dose 5 mg).

Adults: 10–20 mg three times a day, increased if necessary up to 20 mg four times a day; maximum daily dose is 100 mg.

Mechanism of action

Dicycloverine hydrochloride functions as an antimuscarinic by blocking the action of acetylcholine at muscarinic receptors in the smooth muscles of the gastrointestinal tract. This inhibition results in reduced motility and relaxation of the gastrointestinal smooth muscle, alleviating spasms and cramping.

Pharmacodynamics

The primary effect of dicycloverine hydrochloride is the reduction of gut motility due to its antimuscarinic properties. It has a less pronounced antimuscarinic action compared to atropine but may also exhibit some direct relaxant effects on smooth muscle. This dual action helps in relieving abdominal pain associated with smooth muscle spasms.

Pharmacokinetics

Dicycloverine hydrochloride is well absorbed from the gastrointestinal tract. Its onset of action typically occurs within 30 minutes to 1 hour after oral administration, with a duration of effect lasting several hours. The drug undergoes hepatic metabolism and has a variable elimination half-life. Its clearance may be affected by renal function, and caution is advised in patients with renal impairment.

Contra-indications

• Hypersensitivity to dicycloverine or any of its components
• Glaucoma
• Myasthenia gravis
• Severe ulcerative colitis
• Obstructive uropathy
• Severe gastrointestinal obstruction

Adverse effects

• Dry mouth
• Dizziness
• Constipation
• Drowsiness
• Nausea
• Blurred vision
• Urinary retention
• Increased heart rate
• Skin reactions (e.g., flushing, urticaria)

Interactions

• Anticholinergic drugs may enhance effects
• Potentiation of the effects of other CNS depressants such as alcohol
• Antacids containing aluminium may increase risk of toxicity

Precautions

• Use with caution in patients with renal impairment
• May exacerbate conditions like glaucoma and myasthenia gravis
• Monitor for signs of anticholinergic syndrome

Pregnancy

Not known to be harmful; manufacturer advises use only if essential.

Breast-feeding

Avoid; present in milk with potential for causing apnoea in infants.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral solution: Dicycloverine hydrochloride 500 micrograms per 1 ml
• Combination products containing aluminium hydroxide and simeticone

Indications

• Irritable bowel syndrome (IBS)
• Gastrointestinal spasm
• Abdominal cramping

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: 20 mg to 40 mg orally, 4 times daily or 10 mg to 20 mg by intramuscular injection, as needed. Do not administer intravenously.

Mechanism of action

Dicyclomine achieves its action partially through direct antimuscarinic activity at the M1, M3, and M2 receptors, and partially through antagonism of bradykinin and histamine. It non-competitively inhibits the action of bradykinin and histamine, leading to a direct relaxant effect on smooth muscle, specifically reducing the strength of contractions observed in ileal spasms. Its major action appears to be a nonspecific direct relaxant effect on smooth muscle rather than competitive antagonism of acetylcholine.

Pharmacodynamics

Dicyclomine is classified as an anticholinergic agent that relaxes the smooth muscles of the intestines. Its duration of action is relatively short, leading to a typical administration schedule of four times daily, with doses ranging from 20-40 mg orally or 10-20 mg via intramuscular injection. It is important to note that dicyclomine should not be administered intravenously.

Pharmacokinetics

Dicyclomine is absorbed through the gastrointestinal tract and metabolized in the liver. The onset of action occurs within 1 hour of administration, with peak effects seen at approximately 1-2 hours. The elimination half-life varies, but it is generally in the range of 1-2 hours, necessitating multiple daily doses to maintain therapeutic levels. The drug is primarily excreted in urine as metabolites.

Contra-indications

• Glaucoma
• Myasthenia gravis
• Severe ulcerative colitis
• Obstructive uropathy
• Obstructive gastrointestinal disease
• Tachyarrhythmias

Adverse effects

• Dizziness
• Dry mouth
• Nausea
• Vomiting
• Constipation
• Blurred vision
• Tachycardia
• Urinary retention

Interactions

• Clozapine (unknown additive effect)
• Second-generation antipsychotics (unknown additive effect)

Precautions

• Use with caution in patients with renal impairment
• Use with caution in patients with hepatic impairment
• Caution in elderly patients due to increased risk of sensitivity to anticholinergic effects

Pregnancy

Dicyclomine is not recommended during pregnancy due to potential risk to the fetus.

Breast-feeding

Dicyclomine is excreted in breast milk and may cause adverse effects in nursing infants; use with caution.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Oral tablet (20 mg, 40 mg)
• Injection (10 mg, 20 mg)

Indications

• Mild to moderate pain
• Dysmenorrhea
• Postoperative pain
• Osteoarthritis
• Rheumatoid arthritis

Dosage

Children: For

Adults: The usual adult dose is 500 mg initially, followed by 250 mg every 8 hours as needed. The maximum daily dose should not exceed 2000 mg.

Mechanism of action

Mefenamic acid exerts its therapeutic effect by inhibiting the cyclooxygenase (COX) enzymes, which are responsible for the conversion of arachidonic acid to prostaglandins. By reducing prostaglandin production, mefenamic acid decreases inflammation, pain, and fever. This inhibition primarily occurs through the non-selective blockade of COX-1 and COX-2 isoforms.

Pharmacodynamics

The pharmacodynamics of mefenamic acid involve its analgesic, anti-inflammatory, and antipyretic properties. The drug is effective in reducing pain and inflammation due to its ability to lower prostaglandin levels, which play a key role in the inflammatory response. Mefenamic acid tends to have a rapid onset of action, typically within 1 to 2 hours after administration, and its effects can last for several hours, providing relief from pain.

Pharmacokinetics

Mefenamic acid is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 to 4 hours after oral administration. The drug is extensively metabolized in the liver, primarily through glucuronidation, leading to the formation of active and inactive metabolites. It has a relatively long half-life of about 2 to 4 hours, and it is excreted mainly in the urine, both as unchanged drug and as metabolites. The pharmacokinetics can be influenced by factors such as age, liver function, and concurrent medications.

Contra-indications

• Hypersensitivity to mefenamic acid or any of its excipients
• Active or history of peptic ulcer disease
• Severe heart failure
• History of gastrointestinal bleeding or perforation
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea, constipation)
• Headache
• Dizziness
• Rash
• Elevated liver enzymes
• Renal impairment
• Anaphylactic reactions
• Increased risk of cardiovascular events

Interactions

• Increased exposure when used with regorafenib (severe interaction)

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor renal function in patients with compromised renal function
• Caution in patients with cardiovascular diseases
• Caution in the elderly, who may be more susceptible to adverse effects

Pregnancy

Mefenamic acid should be avoided during pregnancy, especially in the third trimester due to risks of fetal cardiovascular effects and potential complications.

Breast-feeding

Use with caution; mefenamic acid is excreted in breast milk, but significant effects on the nursing infant are not expected.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Capsules
• Tablets
• Oral suspension

Mechanism of action

Dicyclomine achieves its action partially through direct antimuscarinic activity of the M1, M3, and M2 receptors; and partially through antagonism of bradykinin and histamine. Dicyclomine non-competitively inhibits the action of bradykinin and histamine, resulting in direct action on the smooth muscle, and decreased strength of contractions seen in spasms of the ileum. ...MAJOR ACTION APPEARS TO BE NONSPECIFIC DIRECT RELAXANT ACTION ON SMOOTH MUSLCE RATHER THAN COMPETITIVE ANTAGONISM OF ACH.

Pharmacodynamics

Dicyclomine is an anticholinergic drug used to relax the smooth muscles of the intestines. It's duration of action is not especially long as it is usually taken 4 times daily with individual doses of 20-40mg orally or 10-20mg by intramuscular injection. Dicyclomine should not be administered intravenously.